Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules

S Kozlowski; M Corr; T Takeshita; L F Boyd; C D Pendleton; R N Germain; J A Berzofsky; D H Margulies

doi:10.1084/jem.175.6.1417

Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules

J Exp Med. 1992 Jun 1;175(6):1417-22. doi: 10.1084/jem.175.6.1417.

Authors

S Kozlowski¹, M Corr, T Takeshita, L F Boyd, C D Pendleton, R N Germain, J A Berzofsky, D H Margulies

Affiliation

¹ Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.

MeSH terms

Amino Acid Sequence
Animals
Captopril / pharmacology
Carboxypeptidases / antagonists & inhibitors
Carboxypeptidases / metabolism
Cell-Free System
Gene Products, env / immunology
Gene Products, env / metabolism*
H-2 Antigens / genetics
H-2 Antigens / immunology*
H-2 Antigens / isolation & purification
HIV Envelope Protein gp160
HIV-1 / immunology*
Histocompatibility Antigen H-2D
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class I / isolation & purification
Humans
Kinetics
L Cells
Mice
Molecular Sequence Data
Peptide Fragments / chemical synthesis
Peptide Fragments / metabolism
Peptidyl-Dipeptidase A / blood*
Protein Precursors / immunology
Protein Precursors / metabolism*
T-Lymphocytes / immunology
Transfection
beta 2-Microglobulin / metabolism

Substances

Gene Products, env
H-2 Antigens
HIV Envelope Protein gp160
Histocompatibility Antigen H-2D
Histocompatibility Antigens Class I
Peptide Fragments
Protein Precursors
beta 2-Microglobulin
Captopril
Carboxypeptidases
Peptidyl-Dipeptidase A